Anemia is a common problem among older adults occurring in over 10% of community dwelling older persons and exceeding 50% among the frail elderly. A consistent and independent relationship exists between anemia and a heightened risk of adverse consequences in the elderly including impaired function, more disability, worse quality of life, greater hospitalization, and higher mortality. The expanding population of older adults and high prevalence of anemia translates into substantial anemia related morbidity and mortality. As a potentially modifiable factor, anemia is a highly promising target for correction. Nevertheless, interventional studies for anemia in older adults are limited. For the majority of cases of anemia in the elderly, a cause can be identified. However, approximately 1/3rd of cases remain "unexplained" after initial diagnostic testing. This "unexplained anemia in the elderly" (UAE) can be clinically defined and also translates into increased mortality. Since the risks and benefits of treatment are unknown, UAE is ideally suited for therapeutic studies. We propose creating the Partnership for Anemia: Clinical and Translational Trials (PACTTE) consortium by partnering the Duke Clinical Research Center as a coordinating center, with a network of sites and accomplished investigators, to design and conduct clinical and translational trials in UAE. To discern the influence of anemia correction in older adults, a uniform panel of geriatric instruments that assess function, quality of life, and cognition will be employed in each trial. Our initial protocol will consist of a randomized treatment trial of (ESA) or placebo among UAE patients 70 years and older. We hypothesize that ESA treatment of UAE will improve self report physical function as measured by the short-form 36 physical component score (SF36-PCS).We believe that hypothesis directed translational studies will lead to key insights that will enable creating a subsequent generation of rationally designed interventional studies. To that end, a biorepository core will be established by obtaining peripheral blood and when available, marrow samples from subjects enrolled on studies. We expect our research will have far-reaching implications ranging from 1) developing a standard panel of geriatric instruments applicable to any anemia interventional trial in older adults 2) determining whether ESA for UAE is safe and adequately improves functional status to justify larger scale clinical trials 3) elucidating major mechanisms leading to UAE that will guide future trials and research. RELEVANCE: For the majority of cases of anemia in the elderly, a cause can be identified. For some, anemia may be corrected by treating the underlying cause. Nevertheless, approximately 1/3rd of anemia cases remain "unexplained" after initial diagnostic testing, representing the largest diagnostic category of anemia. This Unexplained anemia in the elderly (UAA) can be clinically defined and also shows increased mortality. As the risks or benefits of treatment are completely unknown, UAE is ideally suited for interventional trials.